PROJECT SUMMARY Cognitive impairment affects the majority of older adults with end stage renal disease (ESRD) and negatively impacts their quality of life, health care costs, and health outcomes. Our long-term goal is to develop strategies to prevent and treat cognitive impairment in patients with ESRD. Our preliminary data indicate that specific domains of cognition improve with kidney transplantation, with corresponding changes in brain structure. These data indicate potential reversibility in both cognitive impairment and structural brain changes associated with ESRD. In this proposal, we will longitudinally study patients with ESRD before and after kidney transplantation. By comparing baseline cognition and brain MRI findings between ESRD patients and controls, we will more firmly define the domains of cognition that are affected in ESRD, and whether cognitive impairment associated with ESRD corresponds to structural changes in the brain. By comparing cognitive function and brain changes before and after kidney transplantation, we will determine the extent of reversibility in cognition and in accompanying structural changes in the brain that may functionally regulate the improvements in cognition. The proposed research will pinpoint areas of reversibility in cognitive function and brain structural changes in ESRD and identify targets for future therapies. Data from this study will also identify cognitive deficits in both pre- and post- transplant patients with ESRD. This information will have implications in the clinical management of patients with ESRD and the methods used for patient education. This Mentored Patient-Oriented Career Development Award (K23) will provide the PI with the necessary training and expertise in cognitive function assessment, brain imaging, and clinical research through didactic and hands on courses, mentoring, and applied experiences. The PI is a transplant nephrologist who has collaborated with Jeffrey Burns, M.D., the Co-Director of University of Kansas Alzheimer's Disease Center; William Brooks, Ph.D, the Director of the Hoglund Brain Imaging Center, David Johnson, Ph.D, the Director of Neuropsychology at the University of Kansas Alzheimer's Disease Center and Mark Sarnak, M.D., an acclaimed investigator in cognitive impairment in ESRD at the Tufts Medical Center, Boston, MA. This unique combination of expertise makes our group ideal for this study.